Recent studies suggest that adult subgranular zone (SGZ) neurogenesis is required for hippocampal plasticity and antidepressant (AD) efficacy. As such, psychiatric research would greatly benefit from understanding the relationship between AD and SGZ neurogenesis. However, fundamental questions about neurogenesis remain unanswered, particularly in regards to the ability of AD to increase SGZ neurogenesis. Three specific aims are proposed 1: Determine how changes in cell cycle kinetics, progenitor division and survival contribute to AD-induced increase in the number of proliferating SGZ cells. 2: Characterize the differential response to AD of the cell types which contribute to the heterogeneous population of dividing cells in the SGZ. 3: Evaluate the potential of proliferating cells in SGZ to respond directly to BDNF. Analysis of the relationship between AD and neurogenesis will provide much needed insight into how SGZ proliferating cells are regulated. These proposed studies will not only provide important information about AD action - crucial for developing new drugs and understanding depression - but also will provide insight into how adult neurogenesis is regulated - a critical issue for biomedical science as a whole. [unreadable] [unreadable]